Abstract
Transplantable tumors and cell lines have been developed from pheochromocytomas arising in mice with a heterozygous knockout mutation of the neurofibromatosis gene, Nf1. Nf1 encodes a ras-GTPase-activating protein, neurofibromin, and mouse pheochromocytoma (MPC) cells in primary cultures typically show extensive spontaneous neuronal differentiation that may result from the loss of the remaining wild-type allele and defective regulation of ras signaling. However, all MPC cell lines express neurofibromin, suggesting that preservation of the wild-type allele may be required to permit the propagation of MPC cells in vitro. MPC lines differ from PC12 cells in that they express both endogenous phenylethanolamine N-methyltransferase (PNMT) and full-length PNMT reporter constructs. PNMT expression is increased by dexamethasone and by cell-cell contact in suspension cultures. Mouse pheochromocytomas are a new tool for studying genes and signaling pathways that regulate cell growth and differentiation in adrenal medullary neoplasms and are a unique model for studying the regulation of PNMT expression.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenal Gland Neoplasms / genetics*
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Adrenal Gland Neoplasms / metabolism
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Adrenal Gland Neoplasms / pathology
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Animals
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic-Leucine Zipper Transcription Factors
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Cells, Cultured
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DNA-Binding Proteins / metabolism
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Female
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Gene Expression
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Genes, Neurofibromatosis 1*
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Genes, Reporter
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Heterozygote
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Male
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Mice
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Mice, Knockout
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Neoplasm Transplantation
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neurofibromin 1
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Nuclear Proteins / metabolism
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Phenylethanolamine N-Methyltransferase / genetics
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Phenylethanolamine N-Methyltransferase / metabolism
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Pheochromocytoma / genetics*
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Pheochromocytoma / metabolism
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Pheochromocytoma / pathology
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Promoter Regions, Genetic
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RNA, Messenger / biosynthesis
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Receptor, trkA / metabolism
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Reserpine / pharmacology
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Transcription Factors*
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Transfection
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Tumor Cells, Cultured*
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic-Leucine Zipper Transcription Factors
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DNA-Binding Proteins
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Myc associated factor X
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Nerve Tissue Proteins
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Neurofibromin 1
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Nuclear Proteins
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RNA, Messenger
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Transcription Factors
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Max protein, mouse
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Reserpine
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Phenylethanolamine N-Methyltransferase
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Receptor, trkA